Paradoxical bradycardia following the administration of sodium nitroprusside in the rat is abolished by indomethacin.
Severe bradycardia and hypotension associated with the administration of organic nitrates or nitrites has been observed in patients with ischaemic heart disease and hypertension. Experiments were performed on rats to elucidate the mechanism by which these vasodilators may effect their anomalous bradycardia-hypotensive effect. In sodium pentobarbital (50 mg.kg-1, ip) anaesthetised rats of the Wistar strain, hypotension and a paradoxical bradycardia were observed following the intra-arterial injection of 10 microgram.kg-1 sodium nitroprusside or 1 mg.kg-1 arachidonic acid. Bilateral vagotomy abolished the bradycardia to both sodium nitroprusside and arachidonic acid but did not eliminate their hypotensive effects. Indomethacin (5 mg.kg-1) abolished the blood pressure and heart rate responses to arachidonic acid. However, indomethacin abolished only the bradycardia to sodium nitroprusside without reducing its effect on blood pressure. These data suggest that in the rat sodium nitroprusside can stimulate prostaglandin biosynthesis which then initiates a reflex bradycardia.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced / Q000517:prevention & control*; D005292:Ferricyanides / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D009599:Nitroprusside / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D014628:Vagotomy
D001095:Arachidonic Acids; D005292:Ferricyanides; D009599:Nitroprusside; D016718:Arachidonic Acid; D007213:Indomethacin